Recombinant Human Arachidonate 12-lipoxygenase, 12S-type (ALOX12)

Function

Catalyzes the regio and stereo-specific incorporation of molecular oxygen into free and esterified polyunsaturated fatty acids generating lipid hydroperoxides that can be further reduced to the corresponding hydroxy species (PubMed:17493578, PubMed:18311922, PubMed:1851637, PubMed:32404334, PubMed:8319693, PubMed:8500694). Mainly converts arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate) to the specific bioactive lipid (12S)-hydroperoxyeicosatetraenoate/(12S)-HPETE (PubMed:17493578, PubMed:22984144, PubMed:24282679, PubMed:8319693, PubMed:8500694). Through the production of bioactive lipids like (12S)-HPETE it regulates different biological processes including platelet activation (PubMed:8319693, PubMed:8500694). It can also catalyze the epoxidation of double bonds of polyunsaturated fatty acids such as (14S)-hydroperoxy-docosahexaenoate/(14S)-HPDHA resulting in the formation of (13S,14S)-epoxy-DHA (PubMed:23504711). Furthermore, it may participate in the sequential oxidations of DHA ((4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate) to generate specialized pro-resolving mediators (SPMs) like resolvin D5 ((7S,17S)-diHPDHA) and (7S,14S)-diHPDHA, that actively down-regulate the immune response and have anti-aggregation properties with platelets (PubMed:32404334). An additional function involves a multistep process by which it transforms leukotriene A4/LTA4 into the bioactive lipids lipoxin A4/LXA4 and lipoxin B4/LXB4, both are vasoactive and LXA4 may regulate neutrophil function via occupancy of specific recognition sites (PubMed:8250832). Can also peroxidize linoleate ((9Z,12Z)-octadecadienoate) to (13S)-hydroperoxyoctadecadienoate/ (13S-HPODE) (By similarity). Due to its role in regulating both the expression of the vascular endothelial growth factor (VEGF, an angiogenic factor involved in the survival and metastasis of solid tumors) and the expression of integrin beta-1 (known to affect tumor cell migration and proliferation), it can be regarded as protumorigenic (PubMed:16638750, PubMed:22237009, PubMed:9751607). Important for cell survival, as it may play a role not only in proliferation but also in the prevention of apoptosis in vascular smooth muscle cells (PubMed:23578768)

Subcellular Location

Cytoplasm, cytosol; Membrane

Disease Association

Esophageal cancer (ESCR) : A malignancy of the esophagus. The most common types are esophageal squamous cell carcinoma and adenocarcinoma. Cancer of the esophagus remains a devastating disease because it is usually not detected until it has progressed to an advanced incurable stage. [Disease susceptibility may be associated with variants affecting the gene represented in this entry. Gln at position 261 may confer interindividual susceptibility to esophageal cancer (PubMed:17460548)] | Colorectal cancer (CRC) : A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. [Disease susceptibility may be associated with variants affecting the gene represented in this entry. Gln at position 261 may confer interindividual susceptibility to colorectal cancer (PubMed:17460548)]

Tissue Specificity

Expressed in vascular smooth muscle cells

Pathway

Lipid metabolism; hydroperoxy eicosatetraenoic acid biosynthesis

• Yoshimoto T. et al. Molecular cloning and expression of human arachidonate 12-lipoxygenase. — Biochem. Biophys. Res. Commun. (1990)
• Funk C.D. et al. Molecular cloning, primary structure, and expression of the human platelet/erythroleukemia cell 12-lipoxygenase. — Proc. Natl. Acad. Sci. U.S.A. (1990)
• Izumi T. et al. Cloning of the cDNA for human 12-lipoxygenase. — Proc. Natl. Acad. Sci. U.S.A. (1990)
• PubMed: CI-2Q517I3OERJ2S (JAN-)
• Zody M.C. et al. DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage. — Nature (2006)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Yoshimoto T. et al. Structure and chromosomal localization of human arachidonate 12-lipoxygenase gene. — J. Biol. Chem. (1992)
• Funk C.D. et al. Characterization of human 12-lipoxygenase genes. — Proc. Natl. Acad. Sci. U.S.A. (1992)